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Fixed Drug Eruptions

Incidence, Recognition, and Avoidance

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Abstract

Drug eruptions often have nonspecific clinical findings, and the evaluation of the probability of an eruption being a drug-induced event is difficult. A few types of drug eruption do not present such problems, and the fixed drug eruption is one of those whose clinical findings are specific enough to allow a diagnosis.

The fixed drug eruption is a commonly reported type of drug eruption. The incidence of fixed drug eruptions has tended to increase, although the overall number of drug eruption cases has decreased. This is one of the reasons why fixed drug eruptions are familiar to dermatologists.

The most characteristic findings of a fixed drug eruption are recurrence of similar lesions at the same sites and healing with residual hyperpigmentation. The residual hyperpigmentation serves as an indicator of site recognition. Diagnosis is not always easy; for example, as is the case for nonpigmenting fixed drug eruptions, which do not have any residual hyperpigmentation. The development of molecular biology may help to clarify the pathogenesis of fixed drug eruptions, but the reason for their recurrence on the same sites is still unknown.

Identification of the causative drug or drugs is essential for the management of fixed drug eruptions, as it is for other drug eruptions. The causative drug or drugs and cross-reactants should be avoided to prevent recurrence. To date, rechallenge is the most reliable method of identifying causative drugs, but increasingly the use of skin tests has gained the attention of investigators. The validity and the problems of skin tests are discussed, and an approach to the clinical management of fixed drug eruptions is presented.

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References

  1. Arndt K.A., Jick H. Rates of cutaneous reactions to drugs. A report from the Boston Collaborative Drug Surveillance Program. JAMA 1976; 235: 918–922

    Article  PubMed  CAS  Google Scholar 

  2. Bigby M., Jick S., Jick H., et al. Drug-induced cutaneous reactions. A report from the Boston Collaborative Drug Surveillance Program on 15438 consecutive inpatients, 1975 to 1982. JAMA 1986; 256: 3358–3363

    Article  PubMed  CAS  Google Scholar 

  3. Kauppinen K., Alanko K. Oral provocation: uses. Semin Dermatol 1989; 8: 187–191

    PubMed  CAS  Google Scholar 

  4. Langeland J. Exanthema fixum due to ultraviolet radiation. Acta Derm Venereol 1982; 62: 169–171

    PubMed  CAS  Google Scholar 

  5. Del Rio E., Guimaraens D., Aguilar A., et al. Fixed exanthema induced by ultraviolet radiation. Dermatology 1996; 193: 54–55

    Article  PubMed  Google Scholar 

  6. Kelso J.M. Fixed food eruption. J Am Acad Dermatol 1996; 35: 638–639

    Article  PubMed  CAS  Google Scholar 

  7. Orchard D.C., Varigos G.A. Fixed drug eruption to tartrazine. Australas J Dermatol 1997; 38: 212–214

    Article  PubMed  CAS  Google Scholar 

  8. Yanguas I., Oleaga J.M., Gonzalez-Guemes M., et al. Fixed food eruption caused by lentils. J Am Acad Dermatol 1998; 38: 640–641

    Article  PubMed  CAS  Google Scholar 

  9. Puavilai S., Choonhakarn C. Drug eruptions in Bangkok: a 1-year study at Ramathibodi Hospital. Int J Dermatol 1998; 37: 747–751

    Article  PubMed  CAS  Google Scholar 

  10. Mahboob A., Haroon T.S. Drugs causing fixed eruptions: a study of 450 cases. Int J Dermatol 1998; 37: 833–838

    Article  PubMed  CAS  Google Scholar 

  11. Stubb S., Heikkila H., Kauppinen K. Cutaneous reactions to drugs: a series of in-patients during a five-year period. Acta Derm Venereol (Stockh) 1994; 74: 289–291

    CAS  Google Scholar 

  12. Sharma V.K., Dhar S., Clinical pattern of cutaneous drug eruption among children and adolescents in North India. Ped Dermatol 1995; 12: 178–183

    Article  CAS  Google Scholar 

  13. Hunziker Th., Kunzi U.-P., Braunschweig S., et al. Comprehensive hospital drug monitoring (CHDM): adverse skin reactions, a 20-year survey. Allergy 1997; 52: 388–393

    Article  PubMed  CAS  Google Scholar 

  14. Bigby M., Stern R.S., Arndt K.A. Allergic cutaneous reactions to drugs. Prim Care 1989; 16: 713–727

    PubMed  CAS  Google Scholar 

  15. Kuligowski M.E., Chang A., Rathi R. Multiple fixed drug eruption due to ibuprofen. Contact Dermatitis 1991; 25: 259–260

    Article  PubMed  CAS  Google Scholar 

  16. Sehgal V.N., Bhattacharya S.N. Multiple fixed drug eruption (FDE) following continuous cotrimoxazole (TMP + SMZ) therapy. J Dermatol 1997; 24: 410–411

    PubMed  CAS  Google Scholar 

  17. Mizukawa Y., Shiohara T. Fixed drug eruption presenting as erythema dyschromicum perstans: a flare without taking any medications. Dermatology 1998; 197: 383–385

    Article  PubMed  CAS  Google Scholar 

  18. Palungwachira P., Palungwachira P. Fixed drug eruption due to atenolol: a case report. J Med Assoc Thai 1999; 82: 1158–1161

    PubMed  CAS  Google Scholar 

  19. Inserra D.W., Camisa C. Erythema multiforme-like fixed drug eruption. Cutis 1989; 44: 223–225

    PubMed  CAS  Google Scholar 

  20. Sowden J.M., Smith A.G. Multifocal fixed drug eruption mimicking erythema multiforme. Clin Exp Dermatol 1990; 15: 387–388

    Article  PubMed  CAS  Google Scholar 

  21. Baird B.J., De Villez R.L. Widespread bullous fixed drug eruption mimicking toxic epidermal necrolysis. Int J Dermatol 1988; 27: 170–174

    Article  PubMed  CAS  Google Scholar 

  22. Sigal-Nahum M., Konqui A., Gaulier A., et al. Linear fixed drug eruption. Br J Dermatol 1988; 118: 849–851

    Article  PubMed  CAS  Google Scholar 

  23. Ozkaya-Bayazit E., Baykal C. Trimethoprim-induced linear fixed drug eruption. Br J Dermatol 1997; 137: 1028–1029

    Article  PubMed  CAS  Google Scholar 

  24. Grosshans E., Marot L. Blaschkitis in adults. Ann Dermatol Venereol 1990; 117: 9–15

    PubMed  CAS  Google Scholar 

  25. Guin J.D., Haynie L.S., Jackson D., et al. Wandering fixed drug eruption: a mucocutaneous reaction to acetaminophen. J Am Acad Dermatol 1987; 17: 399–402

    Article  PubMed  CAS  Google Scholar 

  26. Shelley W.B., Shelley E.D. Nonpigmenting fixed drug eruption as a distinctive reaction pattern: examples caused by sensitivity to pseudoephedrine hydrochloride and tetrahydrozoline. J Am Acad Dermatol 1987; 17: 403–407

    Article  PubMed  CAS  Google Scholar 

  27. Benson P.M., Giblin W.J., Douglas D.M. Transient, nonpigmenting fixed drug eruption caused by radiopaque contrast media. J Am Acad Dermatol 1990; 23: 379–381

    Article  PubMed  CAS  Google Scholar 

  28. Dereure O., Guilhou J.J. Nonpigmenting fixed drug eruption: a new case due to betahistine. Dermatology 1996; 193: 248–250

    Article  PubMed  CAS  Google Scholar 

  29. Yeo S.N., Kang SJ, Lee A.Y. Nonpigmenting fixed drug eruption to etodolac [in Korean]. Korean J Dermatol 1999; 37(5): 673–675

    Google Scholar 

  30. Roholt N.S., Lapiere J.C., Traczyk T., et al. A nonscarring sublamina densa bullous drug eruption. J Am Acad Dermatol 1995; 32: 367–371

    Article  PubMed  CAS  Google Scholar 

  31. Thankappan T.P., Zachariah J. Drug-specific clinical pattern in fixed drug eruptions. Int J Dermatol 1991; 30: 867–870

    Article  PubMed  CAS  Google Scholar 

  32. Sharma V.K., Dhar S., Gill A.N. Drug related involvement of specific sites in fixed eruptions: a statistical evaluation. J Dermatol 1996; 23: 530–534

    PubMed  CAS  Google Scholar 

  33. Jain V.K., Dixit V.B., Archana. Fixed drug eruption of the oral mucous membrane. Ann Dent 1991; 50: 9–11

    PubMed  CAS  Google Scholar 

  34. Kanwar A.J., Dhar S., Ghosh S., et al. Mucosal fixed drug eruption. Dermatology 1994; 188: 171

    Article  PubMed  CAS  Google Scholar 

  35. Masu S., Seiji M. Pigmentary incontinence in fixed drug eruption. Histologic and electron microscopic findings. J Am Acad Dermatol 1983; 8: 525–532

    Article  PubMed  CAS  Google Scholar 

  36. Stritzler C., Kopf A.W. Fixed drug eruption caused by 8-chlorotheophylline in Dramamine® with clinical and histologic studies. J Invest Dermatol 1960; 34: 319–330

    PubMed  CAS  Google Scholar 

  37. Van Voorhees A., Stenn K.S. Histological phases of Bactrim-induced fixed drug eruption. The report of one case. Am J Dermatopathol 1987; 9: 528–532

    Article  PubMed  Google Scholar 

  38. De Dobbeleer G., Achten G. Fixed drug eruption: ultrastructural study of dyskeratotic cells. Br J Dermatol 1977; 96: 239–244

    Article  PubMed  Google Scholar 

  39. Visa K., Kayhko K., Stubb S., et al. Immunocompetent cells of fixed drug eruption. Acta Derm Venereol 1987; 67: 30–35

    PubMed  CAS  Google Scholar 

  40. Hindsen M., Christensen O.B., Gruic V., et al. Fixed drug eruption: an immunohistochemical investigation of the acute and healing phase. Br J Dermatol 1987; 116: 351–360

    Article  PubMed  CAS  Google Scholar 

  41. Komatsu T., Moriya N., Shiohara T. T cell receptor (TCR) repertoire and function of human epidermal T cells: restricted TCR V alpha-V beta genes are utilized by T cells residing in the lesional epidermis in fixed drug eruption. Clin Exp Dermatol 1996; 104: 343–350

    CAS  Google Scholar 

  42. Teraki Y., Moriya N., Shiohara T. Drug-induced expression of intercellular adhesion molecule-1 on lesional keratinocytes in fixed drug eruption. Am J Pathol 1994; 145: 550–560

    PubMed  CAS  Google Scholar 

  43. Shiohara T., Nickoloff B.J., Sagawa Y., et al. Fixed drug eruption. Expression of epidermal keratinocyte intercellular adhesion molecule-1(ICAM-1). Arch Dermatol 1989; 125: 1371–1376

    Article  PubMed  CAS  Google Scholar 

  44. Yamauchi R., Morita A., Tsuji T. Fixed drug eruption caused by iopamiol, a contrast medium. J Dermatol 1997; 24: 243–245

    PubMed  CAS  Google Scholar 

  45. Alanko K., Stubb S., Reitamo S. Topical provocation of fixed drug eruption. Br J Dermatol 1987; 116: 561–567

    Article  PubMed  CAS  Google Scholar 

  46. Alanko K. Topical provocation of fixed drug eruption. A study of 30 patients. Contact Dermatitis 1994; 31: 25–27

    Article  PubMed  CAS  Google Scholar 

  47. Ozkaya-Bayazit E., Bayazit H., Ozarmagan G. Topical provocation in 27 cases of cotrimoxazole-induced fixed drug eruption. Contact Dermatitis 1999; 41: 185–189

    Article  PubMed  CAS  Google Scholar 

  48. Lee A.Y. Topical provocation in 31 cases of fixed drug eruption: change of causative drugs in 10 years. Contact Dermatitis 1998; 38: 258–260

    Article  PubMed  CAS  Google Scholar 

  49. Lee A.Y., Lee Y.S. Provocation tests in a chlormezanone-induced fixed drug eruption. DICP 1991; 25: 604–605

    PubMed  CAS  Google Scholar 

  50. Watanabe H., Sueki H., Nakada T., et al. Multiple fixed drug eruption caused by iomeprol (lomeron), a nonionic contrast medium. Dermatology 1999; 198: 291–294

    Article  PubMed  CAS  Google Scholar 

  51. Gonzalo Garijo M.A., Bobadilla Gonzalez P. Cutaneous reaction to naproxen. Allergol Immunopathol (Madr) 1996; 24: 89–92

    Google Scholar 

  52. De Barrio M., Tornero P., Prieto A., et al. Recurrent fixed drug eruption caused by citiolone. J Invest Allergol Clin Immunol 1997; 7: 193–194

    Google Scholar 

  53. Garcia J.C., Torre F., Sanchez M., et al. Fixed drug eruption induced by lidocaine and patch testing. J Invest Allergol Clin Immunol 1997; 7: 127–128

    CAS  Google Scholar 

  54. Jimenez I., Anton E., Picans I., et al. Fixed drug eruption from amoxycillin. Allergol Immunopathol (Madr) 1997; 25: 247–248

    CAS  Google Scholar 

  55. Alanko K. Patch testing in cutaneous reactions caused by carbamazepine. Contact Dermatitis 1993; 29: 254–257

    Article  PubMed  CAS  Google Scholar 

  56. Navarro J.A., Audicana M.T., Villas F., et al. Intradermal testing of fixed drug eruption. Allergy 1996; 51: 963–964

    PubMed  CAS  Google Scholar 

  57. Rietschel R.L., Fowler Jr J.F. The role of patch testing. In: Fisher’s contact dermatitis. 4th ed. Baltimore: Williams & Wilkins, 1995: 11–32

    Google Scholar 

  58. Fujimoto Y., Hayakawa R., Suzuki M., et al. Fixed drug eruption due to allylisopropylacetylurea. Contact Dermatitis 1993; 28: 282–284

    Article  PubMed  CAS  Google Scholar 

  59. Smola H., Kruppa A., Hunzelmann N, et al. Identification of dimenhydrinate as the causative agent in fixed drug eruption using patch-testing in previously affected skin. Br J Dermatol 1998; 138: 920–921

    Article  PubMed  CAS  Google Scholar 

  60. Bruynzeel D.P., Maibach H.I. Patch testing in systemic drug eruptions. Clin Dermatol 1997; 15: 479–484

    Article  PubMed  CAS  Google Scholar 

  61. Gomez B., Sastre J., Azofra J., et al. Fixed drug eruption. Allergol Immunopathol (Madr) 1985; 13: 87–91

    CAS  Google Scholar 

  62. Kauppinen K., Kariniemi A.-L. Clinical manifestations and histological characteristics. In: Kauppinen K., Alanko K., Hannuksela M., et al., editors. Skin reactions to drugs. Boca Raton: CRC Press, 1998: 30–31

    Google Scholar 

  63. Sehgal V.N., Rege V.L., Kharangate V.N. Fixed drug eruption caused by medications: a report from India. Int J Dermatol 1978; 7: 78–81

    Article  Google Scholar 

  64. Kanwar A.J., Bharija S.C., Singh M., et al. Ninety eight fixed drug eruptions with provocation tests. Dermatologica 1988; 177: 274–279

    Article  PubMed  CAS  Google Scholar 

  65. Bharija S.C., Belhaj M.S. Fixed drug eruption due to cotrimoxazole. Australas J Dermatol 1989; 30: 43–44

    Article  PubMed  CAS  Google Scholar 

  66. Morelli J.G., Tay Y.-K., Rogers M., et al. Fixed drug eruptions in children. J Pediatr 1999; 134: 365–367

    Article  PubMed  CAS  Google Scholar 

  67. Alanko K., Stubb S., Kauppinen K. Cutaneous drug reactions: clinical types and causative agents. A five-year survey of in-patients (1981-1985). Acta Derm Venereol (Stockh) 1989; 69: 223–226

    CAS  Google Scholar 

  68. Sehgal V.N., Gangwani O.P. Fixed drug eruption. Current concepts. Int J Dermatol 1987; 26: 67–74

    Article  PubMed  CAS  Google Scholar 

  69. Browne S.G. Fixed eruption in deeply pigmented subjects: clinical observations on 350 patients. BMJ 1964; 2: 1041–1044

    Article  PubMed  CAS  Google Scholar 

  70. Tham S.N., Kwok Y.K., Chan H.L. Cross-reactivity in fixed drug eruptions to tetracyclines. Arch Dermatol 1996; 132: 1134–1135

    Article  PubMed  CAS  Google Scholar 

  71. Bargman H. Lack of cross-sensitivity between tetracycline, doxycycline, and minocycline with regard to fixed drug sensitivity to tetracycline. J Am Acad Dermatol 1984; 11: 900–901

    Article  PubMed  CAS  Google Scholar 

  72. Ordoqui E., De Barrio M., Rodriguez V.M., et al. Cross-sensitivity among oxicams in piroxicam-caused fixed drug eruption: two case reports. Allergy 1995; 50: 741–744

    Article  PubMed  CAS  Google Scholar 

  73. Mishra D., Mobashir M., Zaheer M.S. Fixed drug eruption and cross-reactivity between tinidazole and metronidazole. Int J Dermatol 1990; 29: 740

    Article  PubMed  CAS  Google Scholar 

  74. Thami G.P., Kanwan A.J. Fixed drug eruption due to metronidazole and tinidazole without cross-sensitivity to secnidazole. Dermatology 1998; 196: 368

    Article  PubMed  CAS  Google Scholar 

  75. Pasricha J.S., Shukla S.S. Independent lesions of fixed eruption due to two unrelated drugs in the same patient. Br J Dermatol 1979; 101: 361–362

    Article  PubMed  CAS  Google Scholar 

  76. Chan H.L., Tan K.C. Fixed drug eruption to three anticonvulsant drugs: an unusual case of polysensitivity. J Am Acad Dermatol 1997; 36: 259

    Article  PubMed  CAS  Google Scholar 

  77. Bhargava P., Kuldeep C.M., Mathur N.K. Polysensitivity and familial occurrence in fixed drug eruption. Int J Dermatol 1997; 36: 236

    Article  PubMed  CAS  Google Scholar 

  78. Kelso J.M., Keating R.M. Successful desensitization for treatment of a fixed drug eruption to allopurinol. J Allergy Clin Immunol 1996; 97: 1171–1172

    Article  PubMed  CAS  Google Scholar 

  79. Umpierrez A., Cuesta-Herranz J., De Las Heras M., et al. Successful desensitization of a fixed drug eruption caused by allopurinol. J Allergy Clin Immunol 1998; 101: 286–287

    Article  PubMed  CAS  Google Scholar 

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Lee, AY. Fixed Drug Eruptions. Am J Clin Dermatol 1, 277–285 (2000). https://doi.org/10.2165/00128071-200001050-00003

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